X-linked inhibitor of apoptosis protein, BIR2 domain (XIAP-BIR2)

The BIR2 (Baculovirus IAP Repeat 2) domain of the X-linked inhibitor of apoptosis protein (XIAP) is a specialized protein module that plays a dual role in regulating cell death and immune signaling. It is the primary site through which XIAP binds and directly inhibits the effector caspases, caspase-3 and caspase-7, thereby halting the apoptotic cascade and promoting cell survival [PubMed, Frontiers in Oncology]. Additionally, the BIR2 domain functions as a critical scaffold for the kinase RIPK2 within the NOD2 signaling pathway, facilitating the innate immune response to bacterial pathogens [PubMed, EMBO Molecular Medicine]. In oncology, the overexpression of XIAP and its BIR2 domain is associated with resistance to chemotherapy and poor prognosis, as it prevents cancer cells from undergoing programmed cell death [Frontiers in Oncology, PubMed]. Therapeutic strategies targeting this domain include Smac mimetics, which occupy the BIR2 binding groove to displace caspases and sensitize tumors to apoptosis-inducing agents [PubMed]. However, because of its essential role in immune homeostasis, mutations in the BIR2 domain are linked to severe inflammatory conditions, such as X-linked lymphoproliferative syndrome type 2 (XLP2) and refractory inflammatory bowel disease [EMBO Molecular Medicine, PubMed].

Other names

Baculovirus IAP repeat 2 domain of XIAPBIRC4 BIR2 domainIAP3 BIR2 domainhIAP3 BIR2 domainAPI3 BIR2 domain

Antagonism of the IAP-binding motif (IBM) groove to displace effector caspases (Caspase-3/7) and inhibition of the XIAP-RIPK2 interaction to block NOD2-dependent NF-kappaB signaling